Journal
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Volume 140, Issue 1, Pages 61-72Publisher
OXFORD UNIV PRESS INC
DOI: 10.1309/AJCPIV40ISTBXRAX
Keywords
Neuroendocrine tumors; EMT; Snail1; Snail2; Foxc2; E-cadherin; beta-catenin
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Funding
- Obra Social CajAstur
- Red Tematica de Investigacion Cooperativa en Cancer (RTICC)
- FICYT (Fundacion para el fomento en Asturias de la Investigacion Cientifica Aplicada y la Tecnologia)
- Programa Ramon y Cajal
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Objectives: To elucidate the role of epithelial-mesenchymal transition markers in gastroenteropancreatic neuroendocrine tumors (GEE NETs) and the potential usefulness in their clinical management. Methods: One hundred ten GEE NET paraffin-embedded samples were immunohistochemically analyzed for E-cadherin, N-cadherin, beta-catenin, vimentin, Snail1, Snail2, Twist, and Foxc2 protein expression. Results: The 5-year survival rate was reduced for those patients showing high Snail1 protein levels, a cytoplasmic E-cadherin pattern, reduced N-cadherin expression, and loss of E-cadherin/beta-catenin adhesion complex integrity at the cell membrane. Interestingly, high beta-catenin expression was useful in identifying a grade 1 NET subgroup with a favorable clinical course. Importantly, it also helped to discriminate small-cell vs large-cell grade 3 neuroendocrine carcinomas. Conclusions: beta-Catenin and N-cadherin immunohistochemical detection might be a useful tool in the differential diagnosis of small-cell vs large-cell G3 neuroendocrine carcinomas. High Snail1 and Foxc2 expression is associated with the invasion and metastatic spread of GEE NETs.
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